Thyroid function and serum hepatic enzyme activity in dogs after phenobarbital administration

Phenobarbital is the drug of choice for control of canine epilepsy. Phenoba rbital induces hepatic enzyme activity, can be hepatotoxic, and decreases s erum thyroxine (T-4) concentrations in some dogs. The duration of liver enz yme induction and T-4 concentration decreases after discontinuation of phen obarbital is unknown. The purpose of this study was to characterize the cha nges in serum total T-4 (TT4), free T-4 (FT4), thyroid-stimulating hormone (TSH), cholesterol and albumin concentrations, and activities in serum of a lanine aminotransferase (ALT), alkaline phosphatase (ALP), and gamma-glutam yl transferase (GGT) after discontinuation of long-term phenobarbital admin istration in normal dogs. Twelve normal dogs were administered phenobarbita l at a dosage of approximately 4.4-6.6 mg/kg PO q12h for 27 weeks. Blood wa s collected for analysis before and after 27 weeks of phenobarbital adminis tration and then weekly for 10 weeks after discontinuation of the drug. The dogs were clinically normal throughout the study period. Serum ALT and ALP activity and TSH and cholesterol concentrations were significantly higher than baseline at week 27. Serum T-4 and FT4 were significantly lower. Serum albumin and GGT were not changed from baseline at week 27. Changes in esti mate of thyroid function (TT4, FT4, TSH) persisted for 1-4 weeks after disc ontinuation of phenobarbital, whereas changes in hepatic enzyme activity (A LT, ALP) and cholesterol concentration resolved in 3-5 weeks. To avoid fals e positive results, it is recommended that thyroid testing be performed at least 4 weeks after discontinuation of phenobarbital administration. Elevat ed serum activity of hepatic enzymes 6-8 weeks after discontinuation of phe nobarbital may indicate hepatic disease.